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|Gilead Announces Positive Phase 2 Results for GS-9674 in Primary Sclerosing Cholangitis (PSC) at The Liver Meeting® 2018|
– GS-9674 Granted Orphan Drug Designation by the
PSC is a rare, chronic condition that causes the network of ducts that drain bile from the liver to become inflamed and scarred over time. Progressive damage to the bile ducts in patients with PSC can lead to cirrhosis, liver failure, and cholangiocarcinoma (cancer of the bile ducts). Fatigue, pruritus and abdominal discomfort are common symptoms of PSC that can greatly impact patients’ quality of life. There are no approved treatments for PSC.
“Gilead is committed to applying our research expertise in liver disease
to address this debilitating condition which may lead to serious
liver-related complications for PSC patients,” said
In the Phase 2, double-blind, placebo-controlled trial, 52 non-cirrhotic patients with PSC were randomized to receive GS-9674 100 mg (n=22), GS-9674 30 mg (n=20), or placebo (n=10) orally once daily for 12 weeks. After 12 weeks of treatment, patients receiving GS-9674 100 mg demonstrated significant improvements in liver biochemistry tests, with a median reduction in serum alkaline phosphatase (ALP) of 20.5 percent vs. an increase of 3.4 percent with placebo (p=0.029), median reduction in gamma-glutamyl transferase (GGT) of 30.3 percent vs. an increase of 1.1 percent with placebo (p<0.001), median reduction in alanine aminotransferase (ALT) of 49.4 percent vs. 12.9 percent with placebo (p=0.009), and a median reduction in aspartate aminotransferase (AST) of 42.3 percent vs. 10.8 percent with placebo (p=0.019). In both groups treated with GS-9674, reduced serum levels of C4, an intermediate in the synthesis of bile acids, were observed compared with placebo (-23.2 percent in the 100 mg group, p=0.21; and -30.5 percent in the 30 mg group, p=0.024). Reductions in serum bile acids were greatest with the 100 mg dose.
GS-9674 was well tolerated and the incidence of Grade 2 or 3 pruritus was numerically lower with GS-9674 100 mg (13.6 percent) and 30 mg (20 percent) compared with placebo (40 percent). There were no elevations in serum lipids. Treatment was discontinued due to adverse events in three patients treated with GS-9674 100 mg (14 percent), including one discontinuation due to pruritus, and one patient with placebo (10 percent).
A separate analysis of health-related patient-reported outcome measures (PROs) among patients enrolled in the Phase 2 trial demonstrated significant impairment of PRO scores among PSC patients with pruritus or fatigue. In the evaluation, patients treated with GS-9674 100 mg experienced significant improvement of the Primary Biliary Cholangitis – 40 (PBC-40) Emotional score (p=0.04) compared with patients treated with placebo.
“Patients living with PSC urgently need effective and tolerable
treatment options,” said
GS-9674 is an investigational compound and is not approved by the
GS-9674 is an investigational, selective, non-steroidal agonist of the farnesoid X receptor (FXR), a nuclear hormone receptor that is highly expressed in the gastrointestinal tract and liver. FXR is the primary regulator of bile acid synthesis and plays important roles in glucose and lipid metabolism. GS-9674 is being investigated for the treatment of PSC, primary biliary cholangitis (PBC), and advanced fibrosis due to nonalcoholic steatohepatitis (NASH), a chronic and progressive liver disease characterized by fat accumulation and inflammation in the liver, which can lead to scarring or fibrosis. GS-9674 is an investigational agent and its efficacy and safety have not been determined.
This press release includes forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995 that are
subject to risks, uncertainties and other factors, including Gilead’s
ability to complete the clinical trial programs evaluating GS-9674 for
the treatment of primary sclerosing cholangitis in the currently
anticipated timelines, or at all. In addition, there is the possibility
of unfavorable results from additional clinical trials involving
GS-9674. Further, it is possible that Gilead may make a strategic
decision to discontinue development of GS-9674, and as a result, GS-9674
may never be successfully commercialized. These risks, uncertainties and
other factors could cause actual results to differ materially from those
referred to in the forward-looking statements. The reader is cautioned
not to rely on these forward-looking statements. These and other risks
are described in detail in Gilead’s Quarterly Report on Form 10-Q for
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